Population Pharmacokinetics and Exposure-Response of Trametinib, a MEK inhibitor, in Patients with BRAF V600 mutation-positive melanoma

The purpose of this study was to characterize the pharmacokinetics of oral trametinib, a first in class MEK inhibitor, identify covariates, and describe the relationship between exposure and clinical effects in patients with BRAF V600 metastatic melanoma. Trametinib concentrations obtained in three clinical studies were included in the population pharmacokinetic analysis. Trametinib 2 mg once daily was […]

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Informing Pediatric Drug Development: A Selection from Certara’s Best of Blogs

A selection of short essays by Certara’s pediatric drug development experts. Learn about our technologies and strategies for pediatric drug development to inform dose selection, including PK/PD simulations using sparse data analysis and our Simcyp Pediatric Simulator. Certara’s regulatory writing consultancy, Synchrogenix, also offer regulatory strategy for pediatrics.

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Certara’s Best of Blogs 2015

A selection of short essays from our blog, written to empower our customers with biosimulation and regulatory writing solutions in order to help them solve the toughest drug development problems. Certara staff contributions range in topic from pharmacometrics to systems biology to the growing importance of regulatory writing.

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Safety and population pharmacokinetic analysis of intravenous acetaminophen in neonates, infants, children, and adolescents with pain or fever.

The administration of acetaminophen via the oral and rectal routes may be contraindicated in specific clinical settings. Intravenous administration provides an alternative route for fever reduction and analgesia. This phase 1 study of intravenous acetaminophen (Ofirmev, Cadence Pharmaceuticals, Inc., San Diego, CA) in inpatient pediatric patients with pain or fever requiring intravenous therapy was designed […]

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Pharmacokinetic and Pharmacodynamic Modeling to Determine the Human Dose of ST-246(R) to Protect Against Smallpox.

Although smallpox has been eradicated, the United States government considers it a “material threat” and has funded the discovery and development of potential therapeutic compounds. As reported here, the human efficacious dose for one of these compounds, ST-246, was determined using efficacy studies in nonhuman primates (NHPs), together with pharmacokinetic and pharmacodynamic analysis that predicted […]

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Conversion from twice- to once-daily tacrolimus in pediatric kidney recipients: a pharmacokinetic and bioequivalence study.

The objectives of this study were to investigate pharmacokinetic and pharmacogenetic parameters during the conversion on a 1:1 (mg:mg) basis from a twice-daily (Prograf) to once-daily (Advagraf) tacrolimus formulation in pediatric kidney transplant recipients. Twenty-four-hour pharmacokinetic profiles were analyzed before and after conversion in 19 stable renal transplant recipients (age 7–19 years). Tacrolimus pharmacokinetic parameters [area […]

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The Anatomy of a Great Biosimulation Project

Nastya Kassir

In therapeutic areas with tough competition, it is challenging to establish a complete, confident understanding of a drug’s safety and efficacy profile. Any misunderstanding of a drug’s characteristics can derail the entire development program. Biosimulation, also known as model based drug development, uses a number of techniques, such as population PK modeling, model based meta analysis, and PBPK modeling, to help gain a better understanding of a drug’s risk-benefit profile to increase the likelihood of regulatory success. In this blog post, I’ll discuss how I worked with my colleagues to help develop a novel combination therapy for obesity.

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Topics: Drug Safety, Model-based Drug Development, PK/PD Modeling and Simulation

Pediatric Drug Dosing: Tackling Big Problems for Little Patients

Nastya Kassir

The challenges and complexities of pediatric drug development are well recognized. Pharmacometric modeling and simulation (M&S) leverages prior knowledge to support pediatric drug dosing, trial design and regulatory writing for submissions. As the benefits of pharmacometrics for drug development and regulatory decision-making become increasingly well documented, the FDA has challenged the industry to more rigorously apply modeling and simulation to double the success rate of pediatric trials. To highlight the power of this approach, I’ll present a journal article on using population pharmacokinetics (PopPK) and Bayesian methods to develop an optimal sampling strategy to estimate drug exposure.

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Topics: Drug Safety, Model-based Drug Development
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